ISSN: 1308-5727 | E-ISSN: 1308-5735
Volume : 14 Issue : 1 Year : 2022
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Turkish Society for Pediatric Endocrinology and Diabetes
Investigating Genetic Mutations in a Large Cohort of Iranian Patients with Congenital Hyperinsulinism [J Clin Res Pediatr Endocrinol]
J Clin Res Pediatr Endocrinol. 2022; 14(1): 87-95 | DOI: 10.4274/jcrpe.galenos.2021.2021.0071

Investigating Genetic Mutations in a Large Cohort of Iranian Patients with Congenital Hyperinsulinism

Maryam Razzaghy-Azar1, Saeedeh Saeedi3, Sepideh Borhan Dayani1, Samaneh Enayati1, Farzaneh Abbasi4, Somayyeh Hashemian5, Peyman Eshraghi5, Siroos Karimdadi5, Parisa Tajdini4, Rahim Vakili5, Mahsa M. Amoli1, Hanieh Yaghootkar6
1Tehran University of Medical Sciences, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Metabolic Disorders Research Centre, Tehran, Iran
2Iran University of Medical Sciences, H. Aliasghar Hospital, Tehran, Iran
3Tehran University of Medical Sciences, Endocrinology and Metabolism Clinical Sciences Institute, Endocrinology and Metabolism Research Center, Tehran, Iran
4Tehran University of Medical Sciences, Children’s Medical Center Hospital, Growth and Development Research Center, Tehran, Iran
5Mashhad University of Medical Sciences, Faculty of Medicine, Akbar Hospital, Department of Pediatric Diseases, Mashhad, Iran
6University of Exeter, College of Medicine and Health, Genetics of Complex Traits, London; University of Westminster, School of Life Sciences, Research Centre for Optimal Health, London, England; Luleć University of Technology, Department of Health Sciences, Division of Medical Sciences, Luleć, Sweden

INTRODUCTION: Congenital hyperinsulinism (CHI) is the most frequent cause of severe and persistent hypoglycaemia from birth. Understanding the pathophysiology and genetic defects behind hyperinsulinism and its complications provides clues to timely diagnosis and management. The aim of this study was to evaluate the underlying genetic aetiology of a specific Iranian pediatric cohort with CHI.
METHODS: A total of 44 unrelated children, 20 girls and 24 boys, with an initial diagnosis or history of CHI from all regions of Iran were recruited between 2016 and 2019. Targeted next generation sequencing (tNGS) was performed for the genes found in about half of CHI patients.
RESULTS: Mutations were identified in 24 cases (55%). Patients with a confirmed genetic cause were mainly diagnosed below age of one year old (p=0.01), had fewer other syndromic features, excluding seizure, (p=0.03), were less diazoxide responsive (p=0.04) and were more diazoxide unresponsive leading to pancreatectomy (p=0.007) compared to those with no identified mutations. Among 24 patients with identified genetic mutations, 17 (71%) had a mutation in ABCC8, 3 (12%) in KCNJ11, 3 (12%) in HADH, and 1 patient had a mutation in KMT2D. These included five novel mutations in ABCC8, KCNJ11, and KMT2D.
DISCUSSION AND CONCLUSION: This is the biggest genetic study of CHI in Iran. A high frequency of recessive forms of CHI, especially HADH mutations, in our study could be due to a high rate of consanguineous marriage. We recommend tNGS to screen for all the CHI genes.

Keywords: Congenital hyperinsulinism, genetic mutations, diazoxide, targeted next generation sequencing

Maryam Razzaghy-Azar, Saeedeh Saeedi, Sepideh Borhan Dayani, Samaneh Enayati, Farzaneh Abbasi, Somayyeh Hashemian, Peyman Eshraghi, Siroos Karimdadi, Parisa Tajdini, Rahim Vakili, Mahsa M. Amoli, Hanieh Yaghootkar. Investigating Genetic Mutations in a Large Cohort of Iranian Patients with Congenital Hyperinsulinism. J Clin Res Pediatr Endocrinol. 2022; 14(1): 87-95

Corresponding Author: Hanieh Yaghootkar, Iran
Manuscript Language: English
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